DESCRIPTION: (Verbatim from the Applicant's Abstract) The larval lamprey exhibits axonal regeneration and functional recovery following spinal cord lesions. However, the PI has found that by altering the temperature at which animals are maintained, it is possible to produce animals that exhibit either functional or dysfunctional swimming behavior. Thus the lamprey offers the opportunity to study the nature and consequences of dysfunctional regeneration. She has further found anatomical differences between the regenerated systems under the two conditions, specifically in terms of the distribution of serotoninergic axons. Following transections, there is a dramatic increase in serotonin fibers in areas rostral to the lesion, and a dramatic loss in caudal segments. However under conditions that favor recovery, serotonin fibers are more abundant in the caudal segments. She hypothesizes that serotonin fibers are responsible for at least one form of the behavioral differences seen under the different temperature conditions. The PI now proposes to identify the sources of the increased serotonin innervation in rostral segments, and the fate of the lost serotonin in caudal segments. One possibility that will be explored is that the increases in caudal segments is due to collareral sprouting of descending serotonin systems. She will test this hypothesis by evaluating whether the serotonin fibers originate from the brainstem or from dorsal roots. The fate of dopamine fibers will also be evaluated. Other studies will evaluate the functional capabilities of the animals using a sophisticated stochastic phase model to evaluate physiological responses. This technique, which has been developed by the PI, provides a quantitative measure of the degree of coordination between segments. In the same animals, the regenerated fibers will be traced anatomically and using specific markers for GABA and glycine.